WO2003015772A1 - Inhibitors of polyq-aggregation - Google Patents
Inhibitors of polyq-aggregation Download PDFInfo
- Publication number
- WO2003015772A1 WO2003015772A1 PCT/EP2002/007912 EP0207912W WO03015772A1 WO 2003015772 A1 WO2003015772 A1 WO 2003015772A1 EP 0207912 W EP0207912 W EP 0207912W WO 03015772 A1 WO03015772 A1 WO 03015772A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- benzothiazole
- methyl
- phenyl
- amino
- hydroxy
- Prior art date
Links
- WBZCGYISGYMDOQ-UHFFFAOYSA-N Oc1c(C(c2ccccc2Cl)c(c(O)c2)cc(C(c3ccccc3Cl)c(c(O)c3)cc(C(c(cccc4)c4Cl)c(c(O)c4)cc(C5c6ccccc6Cl)c4O)c3O)c2O)cc5c(O)c1 Chemical compound Oc1c(C(c2ccccc2Cl)c(c(O)c2)cc(C(c3ccccc3Cl)c(c(O)c3)cc(C(c(cccc4)c4Cl)c(c(O)c4)cc(C5c6ccccc6Cl)c4O)c3O)c2O)cc5c(O)c1 WBZCGYISGYMDOQ-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0031—Rectum, anus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/02—Suppositories; Bougies; Bases therefor; Ovules
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/04—Drugs for skeletal disorders for non-specific disorders of the connective tissue
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/12—Ophthalmic agents for cataracts
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/08—Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/68—Benzothiazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D277/82—Nitrogen atoms
Definitions
- the invention relates to benzothiazole derivatives of formula
- R is OH, OA or Hal
- R , R° are independently of each other H or A,
- R 2 and R 3 together are an alkylene chain with 4, 5 or 6 C atoms
- R 4 , R 5 are independently of each other A or Hal,
- A is alkyl with 1 , 2, 3, 4, 5 or 6 C atoms
- Hal is F, CI, Br or l, and their pharmaceutically tolerable derivatives, solvates and stereoisomers, with the proviso that the compounds
- the invention relates to the use of a compound of formula I and their pharmaceutically tolerable derivatives, solvates and stereoisomers for the preparation of a pharmaceutical for inhibiting the formation of polyQ-aggregation.
- the invention relates to compounds selected from the group consisting of
- the invention relates to the use of a compound selected from the group consisting of
- the invention was based on the object of finding compounds having valuable properties, in particular those which can be used for the production of medicaments.
- the compounds can be employed as pharmaceutical active compounds in human and veterinary medicine.
- the invention relates to the use of a compound of formula I and their pharmaceutically tolerable derivatives, solvates and stereoisomers for the preparation of a pharmaceutical for the treatment of Huntington's disease.
- the invention relates to the use of a compound selected from the group consisting of 2-amino-7-chloro-6-hydroxy-4-methyl-benzothiazole, 2-amino-4-chloro-6-hydroxy-7-methyl-benzothiazole, 2-amino-6-hydroxy-4-methyl-benzothiazole, 2-amino-5,7-dimethyl-6-hydroxy-benzothiazole, 2-dimethylamino-6-hydroxy-benzothiazole, 2-amino-4,7-dimethyl-6-hydroxy-benzothiazole, 6-methoxy-4,7-dimethyl-benzothiazol-2-ylamine, N-(6-methoxy-4,7-dimethyl-benzothiazol-2-yl)-N-methylamine
- the invention relates to the use of a compound of formula I and their pharmaceutically tolerable derivatives, solvates and stereoisomers for the preparation of a pharmaceutical for the treatment of spinal and bulbar muscular atrophy, dentatorubal pallidoluysian atrophy, spinocerebellar ataxia type-1 , -2, -3, -6 and -7, Alzheimer's disease, bovine spongioform encephalopathy, primary systemic amyloidosis, secondary systemic amyloidosis, senile systemic amyloidosis, familial amyloid polyneuropathy I, hereditary cerebral amyloid angiopathy, hemodialysis-related amyloidosis, familial amyloid polyneuropathy III, Finnish hereditary systemic amyloidosis, type II diabetis, medullary carcinoma of thyroid, spongiform encephalopathies (prion diseases): Kuru, Gerstmann- Straussler-Scheinker syndrome, familial insomnia,
- the invention relates to the use of a compound selected from the group consisting of
- the invention relates to the use of a compound selected from the group consisting of
- the invention relates to the use of a compound selected from the group consisting of
- the invention relates to compounds selected from the group consisting of ⁇ /-(6-phenylcarbamoyl-benzothiazol-2-yl)-terephthalamic acid methyl ester, 3-methoxy- ⁇ /-[4-(6-methyl-benzothiazol-2-yl)-phenyl]-benzamide, 3-amino-/V-[4-(6-methyl-2,3-dihydro-benzothiazol-2-yl)-phenyl]-benzamide, 4-[(4-benzothiazol-2-yl-phenylimino)-methyl]-2,6-dibromo-benzene-1 ,3-diol,
- the invention relates to compounds selected from the group consisting of
- the invention relates to the use of a compound selected from the group consisting of
- the invention relates to the use of a compound selected from the group consisting of
- the invention relates to compounds selected from the group consisting of
- the invention relates to the use of a compound selected from the group consisting of
- the invention relates to the use of a compound selected from the group consisting of
- the compounds mentioned-above are suitable as pharmaceutical active compounds for the treatment of Huntington's disease. They are furthermore suitable for the treatment of spinal and bulbar muscular atrophy, dentatorubal pallidoluysian atrophy, spinocerebellar ataxia type-1 , -2, -3, -6 and -7, Alzheimer's disease, bovine spongioform encephalopathy, primary systemic amyloidosis, secondary systemic amyloidosis, senile systemic amyloidosis, familial amyloid polyneuropathy I, hereditary cerebral amyloid angiopathy, hemodialysis-related amyloidosis, familial amyloid polyneuropathy III, Finnish hereditary systemic amyloidosis, type II diabetis, medullary carcinoma of thyroid, spongiform encephalopathies (prion diseases): Kuru, Gerstmann- Straussler-Scheinker syndrome, familial insomnia, scrapie, atrial amyloidosis, her
- HD exon 1 protein with a polyglutamine sequence in the pathological range (51 and 83 glutamines) is achieved through a tetracycline (tet)-regulated transactivator, a fusion protein consisting of the tet-repressor and a VP16 activation domain.
- tet tetracycline
- This hybrid protein binds specifically to a tetracycline responsive DNA element TRE and promotes transcription from the adjacent CMV promoter.
- Tetracycine and its analogues such as doxycycline can bind to the transactivator and thereby prevent the hybrid protein from binding the TRE element.
- Hydrates and solvates are understood as meaning, for example, the hemi-, mono- or dihydrates, solvates are understood as meaning, for example, alcohol addition compounds such as, for example, with methanol or ethanol.
- pharmaceutically tolerable derivatives is taken to mean, for example, the salts of the compounds according to the invention and also so-called prodrug compounds.
- prodrug derivatives is taken to mean, for example, compounds of the formula I which have been modified with, for example, alkyl or acyl groups, sugars or oligopeptides and which are rapidly cleaved in the organism to give the effective compounds according to the invention.
- prodrug derivatives also include biodegradable polymer derivatives of the compounds according to the invention, as described, for example, in Int. J. Pharm. 115, 61-67 (1995).
- the invention also relates to mixtures of the compounds of the formula I according to the invention, for example mixtures of two diastereomers, for example in the ratio 1:1, 1:2, 1:3, 1 :4, 1:5, 1:10, 1 :100 or 1:1000. These are particularly preferably mixtures of stereoisomeric compounds.
- A is alkyl, is unbranched (linear) or branched, and has 1 , 2, 3, 4, 5 or 6 carbon atoms.
- A is preferably methyl, furthermore ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl or tert-butyl, furthermore also pentyl, 1-, 2- or 3- methylbutyl, 1 ,1- , 1 ,2- or 2,2-dimethylpropyl, 1-ethylpropyl, hexyl, furthermore preferably, for example, trifluoromethyl, pentafluoroethyl or 1 ,1 ,1 -trifluoroethyl.
- the compounds of the present invention and also the starting substances for their preparation are otherwise prepared by methods known per se, such as are described in the literature (e.g. in the standard works such as Houben-Weyl, Methoden der organischen Chemie [Methods of Organic Chemistry], Georg-Thieme-Verlag, Stuttgart), namely under reaction conditions which are known and suitable for the reactions mentioned. Use can also be made in this case of variants which are known per se, but not mentioned here in greater detail.
- Benzothiazoles can also be prepared from anilines via thioureas (obtained according to C.R. Rasmussen Synthesis 1988,456 or Organic Synthesis, volume III, 735 (1955)) and subsequent treatment with sulfinylchloride according to the procedure of Th. Papenfuhs (Angewandte Chemie 94, 544 (1982).
- Suitable inert solvents are, for example, hydrocarbons such as hexane, petroleum ether, benzene, toluene or xylene; chlorinated hydrocarbons such as trichloroethylene, 1 ,2-dichloroethane, carbon tetrachloride, chloroform or dichloromethane; alcohols such as methanol, ethanol, isopropanol, n-propanol, n-butanol or tert-butanol; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran (THF) or dioxane; glycol ethers such as ethylene glycol monomethyl or monoethyl ether (methyl glycol or ethyl glycol), ethylene glycol dimethyl ether (diglyme); ketones such as acetone or butanone; amides such as acetamide, dimethylacetamide, N-methylpyrrolidon
- a base can be converted with an acid into the associated acid addition salt, for example by reaction of equivalent amounts of the base and of the acid in an inert solvent such as ethanol and subsequent evaporation.
- Suitable acids for this reaction are in particular those which yield physiologically acceptable salts.
- inorganic acids can be used, e.g. sulfuric acid, nitric acid, halohydric acids such as hydrochloric acid or hydrobromic acid, phosphoric acids such as orthophosphoric acid, sulfamic acid, furthermore organic acids, in particular aliphatic, alicyclic, araliphatic, aromatic or heterocyclic mono- or polybasic carboxylic, sulfonic or sulfuric acids, e.g.
- compounds can be converted into the corresponding metal salts, in particular alkali metal salts or alkaline earth metal salts, or into the corresponding ammonium salts using bases (e.g. sodium or potassium hydroxide or carbonate).
- bases e.g. sodium or potassium hydroxide or carbonate.
- Physiologically acceptable organic bases such as, for example, ethanolamine, can also be used.
- the invention furthermore relates to the use of the compounds of the present invention and/or their physiologically acceptable salts for the production of pharmaceutical preparations, in particular by a non-chemical route.
- they can be brought into a suitable dose form together with at least one solid, liquid and/or semi-liquid vehicle or excipient and if appropriate in combination with one or more further active compounds.
- the invention furthermore relates to pharmaceutical preparations comprising at least one compound of the formula I and/or one of its pharmaceutically tolerable derivatives, solvates and stereoisomers and optionally excipients and/or adjuvants.
- the invention furthermore relates to pharmaceutical preparations comprising at least a compound selected from the group 2-amino-6-hydroxy-4,7-dimethyl-benzothiazole hydrochloride, 2-amino-6-hydroxy-4,7-dimethyl-benzothiazole methanesulfonate hydrate,
- preparations can be used as medicaments in human or veterinary medicine.
- Possible vehicles are organic or inorganic substances which are suitable for enteral (e.g. oral) or parenteral administration or topical application and do not react with the novel compounds, for example water, vegetable oils, benzyl alcohols, alkylene glycols, polyethylene glycols, glycerol triacetate, gelatin, carbohydrates such as lactose or starch, magnesium stearate, talc and petroleum jelly.
- tablets, pills, coated tablets, capsules, powders, granules, syrups, juices or drops are used for oral administration
- suppositories are used for rectal administration
- solutions, preferably oily or aqueous solutions, furthermore suspensions, emulsions or implants, are used for parenteral administration and ointments, creams or powders are used for topical application, or transdermally in patches.
- the novel compounds can also be lyophilized and the lyophilizates obtained can be used, for example, for the production of injection preparations.
- the preparations indicated can be sterilized and/or can contain excipients such as lubricants, preservatives, stabilizers and/or wetting agents, emulsifiers, salts for influencing the osmotic pressure, buffer substances, colourants, flavourings and/or one or more further active compounds, e.g. one or more vitamins.
- excipients such as lubricants, preservatives, stabilizers and/or wetting agents, emulsifiers, salts for influencing the osmotic pressure, buffer substances, colourants, flavourings and/or one or more further active compounds, e.g. one or more vitamins.
- compositions which are suitable for administration in the form of aerosols or sprays are, for example, solutions, suspensions or emulsions of the active compound in a pharmaceutically acceptable solvent.
- the compounds of the present invention and their physiologically acceptable salts and solvates can be used for the treatment and/or prophylaxis of the diseases or disease conditions indicated above.
- the substances according to the invention are as a rule preferably administered in doses between approximately 0.1 and 100 mg, in particular between 1 and 10 mg, per dose unit.
- the daily dose is preferably between approximately 0.001 and 10 mg/kg of body weight.
- the specific dose for each patient depends on all sorts of factors, for example on the efficacy of the specific compound employed, on the age, body weight, general state of health, sex, on the diet, on the time and route of administration, on the excretion rate, pharmaceutical combination and severity of the particular disorder to which the therapy applies. Oral administration is preferred.
- a solution of 100 g of 2-amino-6-hydroxy-4,7-dimethyl-benzothiazole hydrochloride, 2-amino-6-hydroxy-4,7-dimethyl-benzothiazole methanesulfonate hydrate or 2-amino-7-chlor-6-hydroxy-4-methyl- benzothiazole and 5 g of disodium hydrogenphosphate is adjusted to pH 6.5 using 2N hydrochloric acid in 3 I of double-distilled water, sterile filtered, dispensed into injection vials, lyophilized under sterile conditions and aseptically sealed. Each injection vial contains 5 mg of active compound.
- a mixture of 20 g of 2-amino-6-hydroxy-4,7-dimethyl-benzothiazole hydrochloride, 2-amino-6-hydroxy-4,7-dimethyl-benzothiazole methanesulfonate hydrate or 2-amino-7-chlor-6-hydroxy-4-methyl- benzothiazole is fused with 100 g of soya lecithin and 1400 g of cocoa butter, poured into moulds and allowed to cool. Each suppository contains 20 mg of active compound.
- a solution is prepared from 1 g 2-amino-6-hydroxy-4,7-dimethyl- benzothiazole hydrochloride, 2-amino-6-hydroxy-4,7-dimethyl- benzothiazole methanesulfonate hydrate or 2-amino-7-chlor-6-hydroxy-4- methyl-benzothiazole, 9.38 g of NaH 2 P0 4 • 2 H 2 0, 28.48 g of Na 2 HP0 4 • 12 H 2 0 and 0.1 g of benzalkonium chloride in 940 ml of doubled-distilled water. It is adjusted to pH 6.8, made up to 1 I and sterilized by irradiation. This solution can be used in the form of eye drops.
- Tablets are pressed analogously to Example E and then coated in a customary manner with a coating of sucrose, potato starch, talc, tragacanth and colourant.
- a solution of 2-amino-6-hydroxy-4,7-dimethyl-benzothiazole hydrochloride, 2-amino-6-hydroxy-4,7-dimethyl-benzothiazole methanesulfonate hydrate or 2-amino-7-chlor-6-hydroxy-4-methyl-benzothiazole in 60 I of double- distilled water is sterile filtered, dispensed into ampoules, lyophilized under sterile conditions and aseptically sealed. Each ampoule contains 10 mg of active compound.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Diabetes (AREA)
- Neurosurgery (AREA)
- Hematology (AREA)
- Ophthalmology & Optometry (AREA)
- Physical Education & Sports Medicine (AREA)
- Obesity (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Psychiatry (AREA)
- Urology & Nephrology (AREA)
- Dermatology (AREA)
- Psychology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Anesthesiology (AREA)
- Hospice & Palliative Care (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Hydrogenated Pyridines (AREA)
Abstract
Description
Claims
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10/486,933 US20050124631A1 (en) | 2001-08-13 | 2002-07-17 | Inhibitors of polyq-aggregation |
DE60220678T DE60220678T2 (en) | 2001-08-13 | 2002-07-17 | INHIBITORS OF THE AGGREGATION OF POLYQ |
CA002456868A CA2456868A1 (en) | 2001-08-13 | 2002-07-17 | Inhibitors of polyq-aggregation |
JP2003520731A JP2005512957A (en) | 2001-08-13 | 2002-07-17 | Poly Q-aggregation inhibitors |
EP02764704A EP1416931B1 (en) | 2001-08-13 | 2002-07-17 | Inhibitors of polyq-aggregation |
US11/760,596 US20070259887A1 (en) | 2001-08-13 | 2007-06-08 | Inhibitors of polyq-aggregation |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP01118838 | 2001-08-13 | ||
EP01118838.0 | 2001-08-13 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US11/760,596 Division US20070259887A1 (en) | 2001-08-13 | 2007-06-08 | Inhibitors of polyq-aggregation |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2003015772A1 true WO2003015772A1 (en) | 2003-02-27 |
Family
ID=8178244
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2002/007912 WO2003015772A1 (en) | 2001-08-13 | 2002-07-17 | Inhibitors of polyq-aggregation |
Country Status (8)
Country | Link |
---|---|
US (2) | US20050124631A1 (en) |
EP (1) | EP1416931B1 (en) |
JP (1) | JP2005512957A (en) |
AT (1) | ATE364382T1 (en) |
CA (1) | CA2456868A1 (en) |
DE (1) | DE60220678T2 (en) |
ES (1) | ES2289141T3 (en) |
WO (1) | WO2003015772A1 (en) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005077343A2 (en) * | 2004-02-11 | 2005-08-25 | Max-Delbrück-Centrum für Molekulare Medizin | Novel drugs and diagnostic compositions for use in the treatment and diagnosis of neurodegenerative diseases or amyloid diseases |
CN104788410A (en) * | 2014-01-22 | 2015-07-22 | 中国科学院上海药物研究所 | Phenyl ring-aromatic ring cascaded compound, and preparation method and medical application thereof |
CN111423563A (en) * | 2020-05-25 | 2020-07-17 | 陕西师范大学 | For detecting Fe3+Fused heterocyclic conjugated polymer and preparation method and application thereof |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
BRPI0919079B1 (en) * | 2008-09-23 | 2022-02-15 | Wista Laboratories Ltd | METHODS FOR MARKING PAIRED HELICOIDAL FILAMENTS (PHFS), AND FOR MARKING AGGREGATE TAU, AS WELL AS BINDING COMPOUNDS FOR AGGREGATE TAU MOLECULES |
Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0282971A2 (en) * | 1987-03-16 | 1988-09-21 | Warner-Lambert Company | Substituted 2-aminobenzothiazoles and derivatives useful as cerebrovascular agents |
EP0374041A1 (en) * | 1988-12-15 | 1990-06-20 | Rhone-Poulenc Sante | Medicaments containing 2-benzothiazolamine derivatives, compounds and their preparation |
EP0507318A1 (en) * | 1991-04-04 | 1992-10-07 | Eisai Co., Ltd. | Benzothiazole derivative |
US5348969A (en) * | 1992-04-03 | 1994-09-20 | Bristol-Myers Squibb Company | Diphenyloxazolyl-oxazoles as platelet aggregation inhibitors |
EP0855391A1 (en) * | 1996-08-07 | 1998-07-29 | Snow Brand Milk Products Co., Ltd. | Novel isoquinoline derivatives |
US5795903A (en) * | 1994-10-26 | 1998-08-18 | Rhone-Poulenc Rorer S.A. | 6-polyfluoroalkoxy-and 6-polyfluoroalkyl-2-aminobenzothiazole derivatives |
WO1999065516A1 (en) * | 1998-06-17 | 1999-12-23 | Yeda Research And Development Co. Ltd. | Methods and compositions for treating diseases mediated by transglutaminase activity |
WO2000073282A1 (en) * | 1999-05-28 | 2000-12-07 | Smithkline Beecham Corporation | Il-8 receptor antagonists |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1245974C (en) * | 2000-06-28 | 2006-03-22 | 特瓦制药工业有限公司 | Carvedilol |
-
2002
- 2002-07-17 WO PCT/EP2002/007912 patent/WO2003015772A1/en active IP Right Grant
- 2002-07-17 AT AT02764704T patent/ATE364382T1/en not_active IP Right Cessation
- 2002-07-17 EP EP02764704A patent/EP1416931B1/en not_active Expired - Lifetime
- 2002-07-17 US US10/486,933 patent/US20050124631A1/en not_active Abandoned
- 2002-07-17 ES ES02764704T patent/ES2289141T3/en not_active Expired - Lifetime
- 2002-07-17 JP JP2003520731A patent/JP2005512957A/en active Pending
- 2002-07-17 DE DE60220678T patent/DE60220678T2/en not_active Expired - Lifetime
- 2002-07-17 CA CA002456868A patent/CA2456868A1/en not_active Abandoned
-
2007
- 2007-06-08 US US11/760,596 patent/US20070259887A1/en not_active Abandoned
Patent Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0282971A2 (en) * | 1987-03-16 | 1988-09-21 | Warner-Lambert Company | Substituted 2-aminobenzothiazoles and derivatives useful as cerebrovascular agents |
EP0374041A1 (en) * | 1988-12-15 | 1990-06-20 | Rhone-Poulenc Sante | Medicaments containing 2-benzothiazolamine derivatives, compounds and their preparation |
EP0507318A1 (en) * | 1991-04-04 | 1992-10-07 | Eisai Co., Ltd. | Benzothiazole derivative |
US5348969A (en) * | 1992-04-03 | 1994-09-20 | Bristol-Myers Squibb Company | Diphenyloxazolyl-oxazoles as platelet aggregation inhibitors |
US5795903A (en) * | 1994-10-26 | 1998-08-18 | Rhone-Poulenc Rorer S.A. | 6-polyfluoroalkoxy-and 6-polyfluoroalkyl-2-aminobenzothiazole derivatives |
EP0855391A1 (en) * | 1996-08-07 | 1998-07-29 | Snow Brand Milk Products Co., Ltd. | Novel isoquinoline derivatives |
WO1999065516A1 (en) * | 1998-06-17 | 1999-12-23 | Yeda Research And Development Co. Ltd. | Methods and compositions for treating diseases mediated by transglutaminase activity |
WO2000073282A1 (en) * | 1999-05-28 | 2000-12-07 | Smithkline Beecham Corporation | Il-8 receptor antagonists |
Non-Patent Citations (1)
Title |
---|
PEREIRA, E R, ET AL.: "Syntheses and antimicrobial activities of five-membered ring heterocycles coupled to indole moieties", JOURNAL OF ANTIBIOTICS, vol. 49, no. 4, 1996, pages 380 - 385, XP009003375 * |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005077343A2 (en) * | 2004-02-11 | 2005-08-25 | Max-Delbrück-Centrum für Molekulare Medizin | Novel drugs and diagnostic compositions for use in the treatment and diagnosis of neurodegenerative diseases or amyloid diseases |
WO2005077343A3 (en) * | 2004-02-11 | 2006-01-26 | Max Delbrueck Centrum | Novel drugs and diagnostic compositions for use in the treatment and diagnosis of neurodegenerative diseases or amyloid diseases |
US20090117040A1 (en) * | 2004-02-11 | 2009-05-07 | Max-Delbrug-Centrum Fur Molekulare Medizin | Novel pharmaceutical and diagnostic compositions for use in the treatment and diagnosis of neurodegenerative diseases or amyloid diseases |
US8710088B2 (en) | 2004-02-11 | 2014-04-29 | Max-Delbruck-Centrum Fur Molekulare Medizin | Pharmaceutical and diagnostic compositions for use in the treatment and diagnosis of neurodegenerative diseases or amyloid diseases |
CN104788410A (en) * | 2014-01-22 | 2015-07-22 | 中国科学院上海药物研究所 | Phenyl ring-aromatic ring cascaded compound, and preparation method and medical application thereof |
CN111423563A (en) * | 2020-05-25 | 2020-07-17 | 陕西师范大学 | For detecting Fe3+Fused heterocyclic conjugated polymer and preparation method and application thereof |
Also Published As
Publication number | Publication date |
---|---|
EP1416931A1 (en) | 2004-05-12 |
ATE364382T1 (en) | 2007-07-15 |
ES2289141T3 (en) | 2008-02-01 |
US20070259887A1 (en) | 2007-11-08 |
EP1416931B1 (en) | 2007-06-13 |
US20050124631A1 (en) | 2005-06-09 |
DE60220678D1 (en) | 2007-07-26 |
CA2456868A1 (en) | 2003-02-27 |
JP2005512957A (en) | 2005-05-12 |
DE60220678T2 (en) | 2008-03-06 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
AU2017248556B2 (en) | Thiadiazolidinediones as gsk-3 inhibitors | |
US9790219B2 (en) | Compounds, compositions, and methods for increasing CFTR activity | |
WO2017223188A1 (en) | Compounds, compositions, and methods for increasing cftr activity | |
CA2452609A1 (en) | Thiazole benzamide derivatives and pharmaceutical compositions for inhibiting cell proliferation, and methods for their use | |
RU2654910C2 (en) | Benzylideneguanidine derivatives and therapeutic use thereof for treatment of protein misfolding related diseases | |
WO2010007316A2 (en) | Novel triazolo(4,3-a)pyridine derivatives, process for the preparation thereof, use thereof as medicaments, pharmaceutical compositions and novel use, in particular as met inhibitors | |
BRPI0712017A2 (en) | 5-phenyl-thiazol-2-yl-urea derivatives and use as pi3 kinase inhibitors | |
US20070259887A1 (en) | Inhibitors of polyq-aggregation | |
HUT76062A (en) | Thiazolidines and oxazolidines substituted by a pyridine ring and pharmaceutical compositions containing the same | |
EP2521726B1 (en) | 5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine derivatives as camkii kinases inhibitors for the treatment of cardiovascular diseases | |
US20130225645A1 (en) | Oral formulations for treating metal overload | |
WO2014086478A1 (en) | Inhibitors of malt1 protease | |
JP2004505983A (en) | Pyrazole-thiazole compounds, pharmaceutical compositions containing them, and methods for their use for inhibition of cyclin dependent kinases | |
US20130245001A1 (en) | Heterocyclic inhibitors of histamine receptors for the treatment of disease | |
EP2527322A1 (en) | Carbamyl alkylphenyl disulfide derivatives and their therapeutic uses | |
FR2941229A1 (en) | New triazolo(4,3-a)pyridine derivatives are Met protein kinase inhibitors useful to treat e.g. fibrotic disorders, metabolic disorders, allergies, asthma, thrombosis, retinopathy, psoriasis, rheumatoid arthritis, diabetes and cancer |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ OM PH PL PT RO RU SD SE SG SI SK SL TJ TM TN TR TT TZ UA UG US UZ VN YU ZA ZM ZW Kind code of ref document: A1 Designated state(s): AE AG AL AM AT AU AZ BA BB BG BY BZ CA CH CN CO CR CU CZ DE DM DZ EC EE ES FI GB GD GE GH HR HU ID IL IN IS JP KE KG KP KR LC LK LR LS LT LU LV MA MD MG MN MW MX MZ NO NZ OM PH PL PT RU SD SE SG SI SK SL TJ TM TN TR TZ UA UG US UZ VN YU ZA ZM |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR IE IT LU MC NL PT SE SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG Kind code of ref document: A1 Designated state(s): GH GM KE LS MW MZ SD SL SZ UG ZM ZW AM AZ BY KG KZ RU TJ TM AT BE BG CH CY CZ DK EE ES FI FR GB GR IE IT LU MC PT SE SK TR BF BJ CF CG CI GA GN GQ GW ML MR NE SN TD TG |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
WWE | Wipo information: entry into national phase |
Ref document number: 2002764704 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2456868 Country of ref document: CA |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2003520731 Country of ref document: JP |
|
WWP | Wipo information: published in national office |
Ref document number: 2002764704 Country of ref document: EP |
|
REG | Reference to national code |
Ref country code: DE Ref legal event code: 8642 |
|
WWE | Wipo information: entry into national phase |
Ref document number: 10486933 Country of ref document: US |
|
WWG | Wipo information: grant in national office |
Ref document number: 2002764704 Country of ref document: EP |